P53 and p21 dynamics encode single-cell DNA damage levels, fine-tuning proliferation and shaping population heterogeneity.

ABSTRACT: Cells must accurately and quickly detect DNA damage through a set of checkpoint mechanisms that enable repair and control proliferation. Heterogeneous levels of cellular stress and noisy signaling processes can lead to phenotypic variability but little is known about their role in underlying proliferation heterogeneity. Here we study two previously published single cell datasets and find that cells encode heterogeneous levels of endogenous and exogenous DNA damage to shape proliferation heterogeneity at the population level. Using a comprehensive time series analysis of short- and long-term signaling dynamics of p53 and p21, we show that DNA damage levels are quantitatively translated into p53 and p21 signal parameters in a gradual manner. Analyzing instantaneous proliferation and signalin

SUBMITTER: Gutu N 

PROVIDER: S-EPMC10673849 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature